Proteomic profiling in equine atypical myopathy: new metabolic insights

Equine atypical myopathy (AM) is a seasonal intoxication of grazing equids. In Europe, this poisoning is linked with the ingestion of toxins contained in the seeds and seedlings of the sycamore maple tree (Acer pseudoplatanus). Once ingested, one of the incriminated toxins, hypoglycin A (HGA), is metabolized into methylenecyclopropylacetyl-CoA (MCPA-CoA) which inhibits several steps of the energy production from fatty acid ß-oxidation. This toxin-induced energy deprivation may explain the 74% mortality rate observed. To date, the mechanism of toxicity is not completely elucidated. Indeed, in the same environmental context, some horses are poisoned and others, so-called “co- grazing horses”, remain free of clinical signs while blood tests confirm the ingestion of toxins. With the purpose of improving our understanding of the pathological process, a large-scale study (60 horses) was conducted to highlight the metabolic pathways modified in the context of toxin ingestion by determining proteomic changes occurring in the blood of diseased (HGA+/MCPA+), healthy co- grazing (HGA+/MCPA) and reference horses (HGA-/MCPA-) through a label-free quantitative proteomic study in UHPLC/MS by timsTOF Pro (Bruker). We identified 2736 proteins with 156 showing significant differences between the diseased and co-grazing groups. The proteomic study also reveals substantial changes in the apparently healthy co-grazing group assuming the existence of a subclinical status. The differentially expressed proteins were sorted according to fold enrichment in metabolic pathways such as glycolysis/gluconeogenesis, complement and coagulation cascades and biosynthesis of amino acids revealing new metabolic insights.